tbuckley/cabot-search huggingface dataset:
Efficacy and safety of setmelanotide, a melanocortin-4 receptor agonist, in patients with Bardet-Biedl syndrome and Alström syndrome: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial with an open-label period
Authors: Andrea M Haqq, Wendy K Chung, Hélène Dollfus, Robert M Haws, Gabriel Á Martos-Moreno, Christine Poitou, Jack A Yanovski, Robert S Mittleman, Guojun Yuan, Elizabeth Forsythe, Karine Clément, Jesús Argente
Journal: The Lancet Diabetes & Endocrinology (2022)
Science disconnected: the translational gap between basic science, clinical trials, and patient care in Alzheimer's disease
Authors: Sarah Gregory, Stina Saunders, Craig W Ritchie
Journal: The Lancet Healthy Longevity (2022)

Both research and clinical practice have traditionally centred on the dementia syndrome of Alzheimer's disease rather than its preclinical and prodromal stages.However, there is a strong scientific and ethical impetus to shift focus to earlier disease stages to improve brain health outcomes and help to keep affected individuals symptom-free (dementiafree) for as long as possible.We provide an overview of recent advancements in early detection, drug development, and trial methodology that should be utilised in the development of new therapies for use in brain health clinics.We propose a triad approach to Alzheimer's disease clinical trials, encompassing (1) experimental medicine studies to gather greater knowledge of disease mechanisms, (2) a more comprehensive platform of phase 2 learning trials to inform phase 3 confirmatory trials, and (3) precision medicine involving smaller subgroups of patients with shared characteristics.This triad would ensure that treatment targets are identified accurately, trial methodology focuses on at-risk populations, and sensitive outcome measures capture potential treatment effects.Clinical services around the world must embrace the brain health clinic model so that neurodegenerative diseases can be detected in their earliest phase to quicken drug development pipelines and potentially improve prognosis.
Neurometabolism and Ventricular Dyssynchrony in Patients With Heart Failure and Reduced Ejection Fraction
Authors: Yujie Bai, Mingkai Yun, Binbin Nie, Liang Shan, Wenxian Liu, Marcus Hacker, Shaoping Nie, Yujie Zhou, Sijin Li, Baoci Shan, Xiaoli Zhang, Xiang Li
Journal: Journal of the American College of Cardiology (2022)
WHO working definition of vitality capacity for healthy longevity monitoring
Authors: Ivan Bautmans, Veerle Knoop, Jotheeswaran Amuthavalli Thiyagarajan, Andrea B Maier, John R Beard, Ellen Freiberger, Daniel Belsky, Mylene Aubertin-Leheudre, Christopher Mikton, Matteo Cesari, Yuka Sumi, Theresa Diaz, Anshu Banerjee
Journal: The Lancet Healthy Longevity (2022)
Comparative Risk of Myocarditis/Pericarditis Following Second Doses of BNT162b2 and mRNA-1273 Coronavirus Vaccines
Authors: Zaeema Naveed, Julia Li, James Wilton, Michelle Spencer, Monika Naus, Héctor A. Velásquez García, Jeffrey C. Kwong, Caren Rose, Michael Otterstatter, Naveed Z. Janjua
Journal: Journal of the American College of Cardiology (2022)
Hospitalizations and Mortality in Patients With Secondary Mitral Regurgitation and Heart Failure
Authors: Gennaro Giustino, Anton Camaj, Samir R. Kapadia, Saibal Kar, William T. Abraham, JoAnn Lindenfeld, D. Scott Lim, Paul A. Grayburn, David J. Cohen, Björn Redfors, Zhipeng Zhou, Stuart J. Pocock, Federico M. Asch, Michael J. Mack, Gregg W. Stone
Journal: Journal of the American College of Cardiology (2022)
Estimating causal effects of physical activity and sedentary behaviours on the development of type 2 diabetes in at-risk children from childhood to late adolescence: an analysis of the QUALITY cohort
Authors: Soren Harnois-Leblanc, Marie-Pierre Sylvestre, Andraea Van Hulst, Tracie A Barnett, Marie-Ève Mathieu, Miceline Mesidor, Jennifer J McGrath, Angelo Tremblay, Vicky Drapeau, Gilles Paradis, Mélanie Henderson
Journal: The Lancet Child & Adolescent Health (2022)
Effectiveness of BNT162b2 booster after CoronaVac primary regimen in pregnant people during omicron period in Brazil
Authors: Pilar T V Florentino, Flávia J O Alves, Thiago Cerqueira-Silva, Vinicius de Araújo Oliveira, Juracy B S Júnior, Gerson O Penna, Viviane Boaventura, Guilherme L Werneck, Neil Pearce, Laura C Rodrigues, Mauricio L Barreto, Manoel Barral-Netto, Enny S Paixão
Journal: The Lancet Infectious Diseases (2022)
A systematic review of worldwide causal and correlational evidence on digital media and democracy
Authors: Philipp Lorenz-Spreen, Lisa Oswald, Stephan Lewandowsky, Ralph Hertwig
Journal: Nature Human Behaviour (2022)

Abstract One of today’s most controversial and consequential issues is whether the global uptake of digital media is causally related to a decline in democracy. We conducted a systematic review of causal and correlational evidence ( N = 496 articles) on the link between digital media use and different political variables. Some associations, such as increasing political participation and information consumption, are likely to be beneficial for democracy and were often observed in autocracies and emerging democracies. Other associations, such as declining political trust, increasing populism and growing polarization, are likely to be detrimental to democracy and were more pronounced in established democracies. While the impact of digital media on political systems depends on the specific variable and system in question, several variables show clear directions of associations. The evidence calls for research efforts and vigilance by governments and civil societies to better understand, design and regulate the interplay of digital media and democracy.
Author Correction: Electronic cigarettes versus nicotine patches for smoking cessation in pregnancy: a randomized controlled trial
Authors: Peter Hajek, Dunja Przulj, Francesca Pesola, Chris Griffiths, Robert Walton, Hayden McRobbie, Tim Coleman, Sarah Lewis, Rachel Whitemore, Miranda Clark, Michael Ussher, Lesley Sinclair, Emily Seager, Sue Cooper, Linda Bauld, Felix Naughton, Peter Sasieni, Isaac Manyonda, Katie Myers Smith
Journal: Nature Medicine (2022)
Omission in Data Sharing Statement
Authors: Katy Bell, Lin Zhu, Paul Glasziou
Journal: JAMA Internal Medicine (2022)

JunQing Xie, BSMed, MSc; Albert Prats-Uribe, DPhil; Qi Feng, PhD; YunHe Wang, MSc; Dipender Gill, MD, PhD; Roger Paredes, MD, PhD; Dani Prieto-Alhambra, MD, PhD
Trends in the Use of Opioids vs Nonpharmacologic Treatments in Adults With Pain, 2011-2019
Authors: Kevin T. Pritchard, Jacques Baillargeon, Wei-Chen Lee, Mukaila A. Raji, Yong-Fang Kuo
Journal: JAMA Network Open (2022)

Importance Chronic pain prevalence among US adults increased between 2010 and 2019. Yet little is known about trends in the use of prescription opioids and nonpharmacologic alternatives in treating pain. Objectives To compare annual trends in the use of prescription opioids, nonpharmacologic alternatives, both treatments, and neither treatment; compare estimates for the annual use of acupuncture, chiropractic care, massage therapy, occupational therapy, and physical therapy; and estimate the association between calendar year and pain treatment based on the severity of pain interference. Design, Setting, and Participants A serial cross-sectional analysis was conducted using the nationally representative Medical Expenditure Panel Survey to estimate the use of outpatient services by cancer-free adults with chronic or surgical pain between calendar years 2011 and 2019. Data analysis was performed from December 29, 2021, to August 5, 2022. Exposures Calendar year (2011-2019) was the primary exposure. Main Outcomes and Measures The association between calendar year and mutually exclusive pain treatments (opioid vs nonpharmacologic vs both vs neither treatment) was examined. A secondary outcome was the prevalence of nonpharmacologic treatments (acupuncture, chiropractic care, massage therapy, occupational therapy, and physical therapy). All analyses were stratified by pain type. Results Among the unweighted 46 420 respondents, 9643 (20.4% weighted) received surgery and 36 777 (79.6% weighted) did not. Weighted percentages indicated that 41.7% of the respondents were aged 45 to 64 years and 55.0% were women. There were significant trends in the use of pain treatments after adjusting for demographic factors, socioeconomic status, health conditions, and pain severity. For example, exclusive use of nonpharmacologic treatments increased in 2019 for both cohorts (chronic pain: adjusted odds ratio [aOR], 2.72; 95% CI, 2.30-3.21; surgical pain: aOR, 1.53; 95% CI, 1.13-2.08) compared with 2011. The use of neither treatment decreased in 2019 for both cohorts (chronic pain: aOR, 0.43; 95% CI, 0.37-0.49; surgical pain: aOR, 0.59; 95% CI, 0.46-0.75) compared with 2011. Among nonpharmacologic treatments, chiropractors and physical therapists were the most common licensed healthcare professionals. Conclusions and Relevance Among cancer-free adults with pain, the annual prevalence of nonpharmacologic pain treatments increased and the prevalent use of neither opioids nor nonpharmacologic therapy decreased for both chronic and surgical pain cohorts. These findings suggest that, although access to outpatient nonpharmacologic treatments is increasing, more severe pain interference may inhibit this access.
Viral associations with kidney disease diagnosis and altered kidney metatranscriptome by kidney function
Authors: Changjin Hong, Felix Eichinger, Mohamed G. Atta, Michelle M. Estrella, Derek M. Fine, Michael J. Ross, Christina Wyatt, Tae Hyun Hwang, Matthias Kretzler, John R. Sedor, John F. O’Toole, Aaron W. Miller, Leslie A. Bruggeman
Journal: Kidney International (2022)
Nicotine Addiction and Intensity of e-Cigarette Use by Adolescents in the US, 2014 to 2021
Authors: Stanton Glantz, Abra Jeffers, Jonathan P. Winickoff
Journal: JAMA Network Open (2022)

Importance As e-cigarettes have become more effective at delivering the addictive drug nicotine, they have become the dominant form of tobacco use by US adolescents. Objective To measure intensity of use of e-cigarettes, cigarettes, and other tobacco products among US adolescents and their dependence level over time. Design, Setting, and Participants This survey study analyzed the cross-sectional National Youth Tobacco Surveys from 2014 to 2021. Confirmatory analysis was conducted using Youth Behavioral Risk Factor Surveillance System from 2015 to 2019. The surveys were administered to national probability samples of US students in grades 6 to 12. Exposures Use of e-cigarettes and other tobacco products before and after the introduction of e-cigarettes delivering high levels of nicotine. Main Outcomes and Measures First tobacco product used, age at initiation of use, intensity of use (days per month), and nicotine addiction (measured as time after waking to first use of any tobacco product). Results A total of 151 573 respondents were included in the analysis (51.1% male and 48.9% female; mean [SEM] age, 14.57 [0.03] years). Prevalence of e-cigarette use peaked in 2019 and then declined. Between 2014 and 2021, the age at initiation of e-cigarette use decreased, and intensity of use and addiction increased. By 2017, e-cigarettes became the most common first product used (77.0%). Age at initiation of use did not change for cigarettes or other tobacco products, and changes in intensity of use were minimal. By 2019, more e-cigarette users were using their first tobacco product within 5 minutes of waking than for cigarettes and all other products combined. Median e-cigarette use also increased from 3 to 5 d/mo in 2014 to 2018 to 6 to 9 d/mo in 2019 to 2020 and 10 to 19 d/mo in 2021. Conclusions and Relevance The changes detected in this survey study may reflect the higher levels of nicotine delivery and addiction liability of modern e-cigarettes that use protonated nicotine to make nicotine easier to inhale. The increasing intensity of use of modern e-cigarettes highlights the clinical need to address youth addiction to these new high-nicotine products over the course of many clinical encounters. In addition, stronger regulation, including comprehensive bans on the sale of flavored tobacco products, should be implemented.
Human type I IFN deficiency does not impair B cell response to SARS-CoV-2 mRNA vaccination
Authors: Aurélien Sokal, Paul Bastard, Pascal Chappert, Giovanna Barba-Spaeth, Slim Fourati, Alexis Vanderberghe, Pauline Lagouge-Roussey, Isabelle Meyts, Adrian Gervais, Magali Bouvier-Alias, Imane Azzaoui, Ignacio Fernández, Andréa de la Selle, Qian Zhang, Lucy Bizien, Isabelle Pellier, Agnès Linglart, Anya Rothenbuhler, Estelle Marcoux, Raphael Anxionnat, Nathalie Cheikh, Juliane Léger, Blanca Amador-Borrero, Fanny Fouyssac, Vanessa Menut, Jean-Christophe Goffard, Caroline Storey, Caroline Demily, Coralie Mallebranche, Jesus Troya, Aurora Pujol, Marie Zins, Pierre Tiberghien, Paul E. Gray, Peter McNaughton, Anna Sullivan, Jane Peake, Romain Levy, Laetitia Languille, Carlos Rodiguez-Gallego, Bertrand Boisson, Sébastien Gallien, Bénédicte Neven, Marc Michel, Bertrand Godeau, Laurent Abel, Felix A. Rey, Jean-Claude Weill, Claude-Agnès Reynaud, Stuart G. Tangye, Jean-Laurent Casanova, Matthieu Mahévas
Journal: The Journal of Experimental Medicine (2022)

Inborn and acquired deficits of type I interferon (IFN) immunity predispose to life-threatening COVID-19 pneumonia. We longitudinally profiled the B cell response to mRNA vaccination in SARS-CoV-2 naive patients with inherited TLR7, IRF7, or IFNAR1 deficiency, as well as young patients with autoantibodies neutralizing type I IFNs due to autoimmune polyendocrine syndrome type-1 (APS-1) and older individuals with age-associated autoantibodies to type I IFNs. The receptor-binding domain spike protein (RBD)–specific memory B cell response in all patients was quantitatively and qualitatively similar to healthy donors. Sustained germinal center responses led to accumulation of somatic hypermutations in immunoglobulin heavy chain genes. The amplitude and duration of, and viral neutralization by, RBD-specific IgG serological response were also largely unaffected by TLR7, IRF7, or IFNAR1 deficiencies up to 7 mo after vaccination in all patients. These results suggest that induction of type I IFN is not required for efficient generation of a humoral response against SARS-CoV-2 by mRNA vaccines.
Can Kidney Organoid Xenografts Accelerate Therapeutic Development for Genetic Kidney Disorders?
Authors: Ting-Chun Kuo, Dalia N. Cabrera-Barragan, Marta Lopez-Marfil, Diana O. Lopez-Cantu, Dario R. Lemos
Journal: Journal of the American Society of Nephrology (2022)

A number of genetic kidney diseases can now be replicated experimentally, using kidney organoids generated from human pluripotent stem cells. This methodology holds great potential for drug discovery. Under in vitro conditions, however, kidney organoids remain developmentally immature, develop scarce vasculature, and may contain undesired off-target cell types. Those critical deficiencies limit their potential as disease-modeling tools. Orthotopic transplantation under the kidney capsule improves the anatomic maturity and vascularization of kidney organoids, while reducing off-target cell content. The improvements can translate into more accurate representations of disease phenotypes and mechanisms in vivo . Recent studies using kidney organoid xenografts highlighted the unique potential of this novel methodology for elucidating molecular mechanisms driving monogenic kidney disorders and for the development ofnovel pharmacotherapies.
A randomized clinical trial of lipid metabolism modulation with fenofibrate for acute coronavirus disease 2019
Authors: Julio A. Chirinos, Patricio Lopez-Jaramillo, Evangelos J. Giamarellos-Bourboulis, Gonzalo H. Dávila-del-Carpio, Abdul Rahman Bizri, Jaime F. Andrade-Villanueva, Oday Salman, Carlos Cure-Cure, Nelson R. Rosado-Santander, Mario P. Cornejo Giraldo, Luz A. González-Hernández, Rima Moghnieh, Rapti Angeliki, María E. Cruz Saldarriaga, Marcos Pariona, Carola Medina, Ioannis Dimitroulis, Charalambos Vlachopoulos, Corina Gutierrez, Juan E. Rodriguez-Mori, Edgar Gomez-Laiton, Rosa Cotrina Pereyra, Jorge Luis Ravelo Hernández, Hugo Arbañil, José Accini-Mendoza, Maritza Pérez-Mayorga, Charalampos Milionis, Garyfallia Poulakou, Gregorio Sánchez, Renzo Valdivia-Vega, Mirko Villavicencio-Carranza, Ricardo J. Ayala-García, Carlos A. Castro-Callirgos, Rosa M. Alfaro Carrasco, Willy Garrido Lecca Danos, Tiffany Sharkoski, Katherine Greene, Bianca Pourmussa, Candy Greczylo, Juan Ortega-Legaspi, Douglas Jacoby, Jesse Chittams, Paraskevi Katsaounou, Zoi Alexiou, Styliani Sympardi, Nancy K. Sweitzer, Mary Putt, Jordana B. Cohen, Ciro Barrantes Alarcón, Denisse Marylyn Mendoza Sanchez, Eduardo Francisco Bernales Salas, Claudia Jesús Chamby Díaz, Ursula Milagros Vargas Gómez, Cynthia Daniela Salinas Herrera, Naldy Lidia Barriga Triviños, Johanna Carolina Coacalla Guerra, Evelyn Marrón Veria, Preethi William, Hugo Espinoza-Rojas, Irwing Renato Benites-Flores, Pedro Antonio Segura-Saldaña
Journal: Nature Metabolism (2022)
Association Between Racial Wealth Inequities and Racial Disparities in Longevity Among US Adults and Role of Reparations Payments, 1992 to 2018
Authors: Kathryn E. W. Himmelstein, Jourdyn A. Lawrence, Jaquelyn L. Jahn, Joniqua N. Ceasar, Michelle Morse, Mary T. Bassett, Bram P. Wispelwey, William A. Darity, Atheendar S. Venkataramani
Journal: JAMA Network Open (2022)

In the US, Black individuals die younger than White individuals and have less household wealth, a legacy of slavery, ongoing discrimination, and discriminatory public policies. The role of wealth inequality in mediating racial health inequities is unclear.To assess the contribution of wealth inequities to the longevity gap that exists between Black and White individuals in the US and to model the potential effects of reparations payments on this gap.This cohort study analyzed the association between wealth and survival among participants in the Health and Retirement Study, a nationally representative panel study of community-dwelling noninstitutionalized US adults 50 years or older that assessed data collected from April 1992 to July 2019. Participants included 7339 non-Hispanic Black (hereinafter Black) and 26 162 non-Hispanic White (hereinafter White) respondents. Data were analyzed from January 1 to September 17, 2022.Household wealth, the sum of all assets (including real estate, vehicles, and investments), minus the value of debts.The primary outcome was all-cause mortality by the end of survey follow-up in 2018. Using parametric survival models, the associations among household wealth, race, and survival were evaluated, adjusting for age, sex, number of household members, and marital status. Additional models controlled for educational level and income. The survival effects of eliminating the current mean wealth gap with reparations payments ($828 055 per household) were simulated.Of the 33 501 individuals in the sample, a weighted 50.1% were women, and weighted mean (SD) age at study entry was 59.3 (11.1) years. Black participants' median life expectancy was 77.5 (95% CI, 77.0-78.2) years, 4 years shorter than the median life expectancy for White participants (81.5 [95% CI, 81.2-81.8] years). Adjusting for demographic variables, Black participants had a hazard ratio for death of 1.26 (95% CI, 1.18-1.34) compared with White participants. After adjusting for differences in wealth, survival did not differ significantly by race (hazard ratio, 1.00 [95% CI, 0.92-1.08]). In simulations, reparations to close the mean racial wealth gap were associated with reductions in the longevity gap by 65.0% to 102.5%.The findings of this cohort study suggest that differences in wealth are associated with the longevity gap that exists between Black and White individuals in the US. Reparations payments to eliminate the racial wealth gap might substantially narrow racial inequities in mortality.
Error in Abstract
Authors: Mytien Nguyen, Mayur Desai, Dowin Boatright
Journal: JAMA Pediatrics (2022)

Atsuyuki Watanabe, MD; Jun Yasuhara, MD; Masao Iwagami, MD, PhD; Yoshihisa Miyamoto, MD; Yuji Yamada, MD; Yukio Suzuki, MD, PhD; Hisato Takagi, MD, PhD; Toshiki Kuno, MD, PhD
Evaluation of Cannabis Use Among US Adults During the COVID-19 Pandemic Within Different Legal Frameworks
Authors: Joshua C. Black, Elise Amioka, Janetta L. Iwanicki, Richard C. Dart, Andrew A. Monte
Journal: JAMA Network Open (2022)

This cross-sectional study analyzes the prevalence of cannabis use by US adults during the COVID-19 pandemic within different legal frameworks and evaluates differences in associated behaviors.
Rare, convergent antibodies targeting the stem helix broadly neutralize diverse betacoronaviruses
Authors: Cherrelle Dacon, Linghang Peng, Ting-Hui Lin, Courtney Tucker, Chang-Chun D Lee, Yu Cong, Lingshu Wang, Lauren Purser, Andrew J R Cooper, Jazmean K Williams, Chul-Woo Pyo, Meng Yuan, Ivan Kosik, Zhe Hu, Ming Zhao, Divya Mohan, Mary Peterson, Jeff Skinner, Saurabh Dixit, Erin Kollins, Louis Huzella, Donna Perry, Russell Byrum, Sanae Lembirik, Michael Murphy, Yi Zhang, Eun Sung Yang, Man Chen, Kwanyee Leung, Rona S Weinberg, Amarendra Pegu, Daniel E Geraghty, Edgar Davidson, Benjamin J Doranz, Iyadh Douagi, Susan Moir, Jonathan W Yewdell, Connie Schmaljohn, Peter D Crompton, John R Mascola, Michael R Holbrook, David Nemazee, Ian A Wilson, Joshua Tan
Journal: Cell Host & Microbe (2022)

Humanity has faced three recent outbreaks of novel betacoronaviruses, emphasizing the need to develop approaches that broadly target coronaviruses. Here, we identify 55 monoclonal antibodies from COVID-19 convalescent donors that bind diverse betacoronavirus spike proteins. Most antibodies targeted an S2 epitope that included the K814 residue and were non-neutralizing. However, 11 antibodies targeting the stem helix neutralized betacoronaviruses from different lineages. Eight antibodies in this group, including the six broadest and most potent neutralizers, were encoded by IGHV1-46 and IGKV3-20. Crystal structures of three antibodies of this class at 1.5-1.75-Å resolution revealed a conserved mode of binding. COV89-22 neutralized SARS-CoV-2 variants of concern including Omicron BA.4/5 and limited disease in Syrian hamsters. Collectively, these findings identify a class of IGHV1-46/IGKV3-20 antibodies that broadly neutralize betacoronaviruses by targeting the stem helix but indicate these antibodies constitute a small fraction of the broadly reactive antibody response to betacoronaviruses after SARS-CoV-2 infection.
Damaging missense variants in IGF1R implicate a role for IGF-1 resistance in the etiology of type 2 diabetes
Authors: Eugene J. Gardner, Katherine A. Kentistou, Stasa Stankovic, Samuel Lockhart, Eleanor Wheeler, Felix R. Day, Nicola D. Kerrison, Nicholas J. Wareham, Claudia Langenberg, Stephen O'Rahilly, Ken K. Ong, John R.B. Perry
Journal: Cell Genomics (2022)

Type 2 diabetes (T2D) is a heritable metabolic disorder. While population studies have identified hundreds of common genetic variants associated with T2D, the role of rare (frequency < 0.1%) protein-coding variation is less clear. We performed exome sequence analysis in 418,436 (n = 32,374 T2D cases) individuals in the UK Biobank. We identified previously reported genes (